IACC Autism Spectrum Disorder Research Portfolio Analysis: Project Listing
Project Id Project Number Sub Project Number Funder Principal Investigator Project Title Project Description Fiscal Year Funding Category Strategic Plan Objective Objective Status Code Arra Funded? Federal/Private Institution State/Country Project Status Web Link 1 Web Link 2 Web Link 3 Active Current Award Period
Project Id: 3521 3689 None Autism Speaks Barnes, Gregory Relation of sleep epileptiform discharges to insomnia and daytime behavior Children with autism spectrum disorders (ASD) are known to have a higher prevalence of epilepsy and sleep disturbances, which may affect daytime functioning. Interictal epileptiform discharges (IEDs) are patterns of abnormal brain activity associated with epilepsy which have also been found to be prevalent in people with ASDs. Whether IEDs are involved in sleep disturbance in children with ASD is unknown, and this proposed study is aimed at examining potential links between IEDs, sleep, and behavior. Researchers will test the hypothesis that IEDs during sleep may affect sleep patterns, contributing to the underlying sleep disturbance which may in turn result in behavioral problems. Dr. Barnes and colleagues will examine the prevalence of IEDs during sleep in a cohort of children with ASD. IEDs are measured by electroencephalography (EEG), which records electrical activity in the brain in a noninvasive manner. EEG and behavioral data will be used to examine the relationships between sleep IEDs, sleep disturbances, and daytime behavior in these children. $0.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Private Vanderbilt University Tennessee Ongoing http://www.autismspeaks.org/science/grants/relation-sleep-epileptiform-discharges-insomnia-and-daytime-behavior?destination=science%2Fgrant-search%2Fresults%2FRelation+of+sleep+epileptiform+discharges+to+insomnia+and+daytime+behavior No URL available. No URL available. active 2009-2010
Project Id: 3526 5P50HD055782-04 4 National Institutes of Health Dager, Stephen ACE Center: Structural and chemical brain imaging of autism This grant provides support for an NIH Autism Center of Excellence (ACE). This study seeks to identify early manifestations of abnormal brain development in autism spectrum disorders (ASD). Twelve-month old infant siblings of children with autism, and comparison non-risk infants, will be studied using magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI), and relationships between brain measures and clinical course and symptom onset will be examined. A second part of the research will examine children entering adolescence in order to identify brain developmental changes that may be related to onset seizure and behavioral decline during the adolescent period. This study will enable understanding of the relationship between variations in brain development and longer-term clinical outcome, focusing on adolescent seizure onset and cognitive decline. $514,982.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Federal University of Washington Washington Ongoing http://projectreporter.nih.gov/project_info_description.cfm?aid=8129667&icde=8970166 No URL available. No URL available. active 2007-2012
Project Id: 3527 5R01NS065020-02 None National Institutes of Health Danzer, Steve Selective disruption of hippocampal dentate granule cells in autism: Impact of PTEN deletion During the development of a child, most brain cells are generated before birth. There is one group of brain cells, however, that are generated in large numbers in infancy. This occurs in a brain region called the hippocampus. These cells are important for the normal development of memory, cognition and language, and disruption of these cells is present in children with autism. The proposed studies seek to better elucidate the causes of autism by determining whether selective disruption of late-generated neurons - specifically hippocampal dentate granule cells - contributes to key features of autism. This will be achieved using a novel combination of transgenic mice to selectively eliminate a gene, PTEN, implicated in autism, from these late-generated neurons. Significantly, although the proximal cause of autism remains to be determined in most cases, the late generation of these neurons (in the late embryonic period and in infancy) may make them uniquely vulnerable to a variety of insults faced by the newborn child (e.g. infection). The proposal will also examine the role of granule cells in the development of epilepsy, the condition most commonly associated with autism. Demonstrating that these cells play an important role in the development of autism (or associated conditions like epilepsy), will provide a compelling rationale to develop new therapies to protect these vulnerable cells. $371,250.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Federal Cincinnati Children's Hospital Medical Center Ohio Ongoing http://projectreporter.nih.gov/project_info_description.cfm?aid=7816937&icde=8914715 No URL available. No URL available. active 2009-2014
Project Id: 3224 n/a None Center for Autism and Related Disorders Dixon, Dennis Evaluation of sleep disturbance in children with ASD This study assesses the prevalence and severity of sleep disturbance in children with autism spectrum disorders (ASD). $27,456.00 Biology Question 2: Other Dot not applicable No Private Center for Autism and Related Disorders (CARD) California Ongoing No URL available. No URL available. No URL available. active 2009-2011
Project Id: 3523 AR080107 None Department of Defense Duffey, Michael Gastrointestinal functions in autism Autism is defined by behavioral patterns and delays in language development, but chronic gastrointestinal (GI) problems are also seen, like abdominal pain, diarrhea, constipation, esophagitis, and gaseousness. The central hypothesis of this proposal is that altered handling of intracellular calcium ion by GI nerve and muscle causes some of these GI disorders. To study these disorders, we will use a genetically altered mouse that exhibits the rare disorder of Timothy Syndrome (TS). Individuals with TS have a genetic mutation in a cell membrane calcium ion channel, known as Cav1.2. Strikingly, over 80% of patients carrying this mutation have also been diagnosed with autism. No other human mutation shows this high degree of correlation. We hypothesize that this mutation in TS mice will cause nerve and muscle cells to be overloaded with calcium ion. Specifically, we will examine intestinal smooth muscle in TS mice to determine if intracellular calcium ion overload alters its ability to propel food. We will also determine if nerves of the intestine abnormally regulate the absorption processes. Next, we will use molecular biological techniques to identify mutant Cav1.2 channels in intestinal smooth muscle and nerves of TS mice and electro-physiological techniques to determine the mechanisms that lead to altered function of these channels. Study of this unique mouse will provide key insights into the cellular basis of autism and its relationship to GI disorders and will provide a model for testing new therapies. $0.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Federal University at Buffalo, The State University of New York New York Ongoing http://cdmrp.army.mil/search.aspx No URL available. No URL available. active 2009-2011
Project Id: 3533 177985 None Simons Foundation O'Hara, Ruth Characterizing sleep disorders in autism spectrum disorder Sleep problems are a common feature of autism spectrum disorders. Impaired sleep causes significant distress to both patient and caregiver and may lead to, and exacerbate, the cognitive and behavioral core symptoms of autism. Sleep disturbances can reflect a wide range of sleep disorders, such as insomnia, circadian rhythm disturbance, periodic limb movement, sleep apnea and rapid eye movement sleep disturbance. Some of these can be effectively alleviated through treatment. Characterizing the type and severity of sleep disorders in people with autism is essential for an effective treatment approach. Still, in this patient population, it has proven difficult to obtain objective overnight measures of sleep by polysomnogram, which involves connecting the person to electrodes that monitor many body functions during sleep. Using a combination of standard and novel objective assessments of sleep, Ruth O'Hara and her colleagues at Stanford University aim to characterize the range and type of sleep disorders experienced by 80 participants on the autism spectrum, aged 6 to18 years. They also plan to examine the impact of various sleep disorders of differing severity on cognitive and behavioral symptoms. Finally, their work aims to improve upon current approaches to polysomnography, including a single-channel sleep electrode (for encephalography) and a SensorBed Mattress, which may be a more user-friendly method to assess sleep disturbances. The researchers have significant expertise in the area of sleep disorders and their impact on cognitive processes in older patients with cognitive impairment and dementia. O'Hara serves on the sleep disorders in psychiatric illnesses workgroup for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. She plans to extend her research on sleep and cognition to the field of autism. $37,354.50 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Private Stanford University California New http://sfari.org/funding/grants/abstracts/characterizing-sleep-disorders-in-autism-spectrum-disorder No URL available. No URL available. active 2010-2012
Project Id: 3522 6213 None Autism Speaks Stickgold, Robert The effects of disturbed sleep on sleep-dependent memory consolidation and daily function in individuals with ASD Autism Spectrum Disorders (ASDs) are associated with disturbed sleep and p articularly with difficulties initiating and maintaining sleep (i.e., insomnia). The severity of these sleep disturbances correlates with increased emotional and attentional problems and more aggressive behavior. This study focuses on brain regions underlying altered social behavior in autism that are normally responsible for the ability to understand the mental states of others. Given the now overwhelming evidence that sleep plays a critical role in learning and memory, and particularly procedural learning, investigations of the role of abnormal sleep in the cognitive, emotional, social and behavioral deficits of ASD are of great importance. The primary goal of this study is to investigate the hypothesis that impaired sleep-dependent emotional and memory processing due to poor sleep plays a key role in the cognitive and behavioral deficits seen in children with ASD and make it difficult for them to benefit from remedial interventions. Specifically, the study will determine whether poor sleep in children with ASD, measured polysomnographically in the laboratory, correlates with impaired sleep-dependent consolidation of probabilistic category learning, as well as with poorer performance on a range of cross-sectional measures of cognitive function, emotional stability, repetitive behaviors and social skills. This will be the first study of sleep-dependent consolidation of learning and memory in ASD. This work will be important in understanding the phenotype of ASD and is a critical first step to designing interventions to improve sleep and daily functioning in individuals with ASD. $112,327.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Private Beth Israel Deaconess Medical Center Massachusetts New http://www.autismspeaks.org/science/grants/effects-disturbed-sleep-sleep-dependent-memory-consolidation-and-daily-function-indiv?destination=science%2Fgrant-search%2Fresults%2Fstickgold No URL available. No URL available. active 2010-2013
Project Id: 3532 2R01HD044763-06A1 None National Institutes of Health Symons, Frank Sensory mechanisms and self-injury Little is known about the sensory and neurobiological basis of chronic self-injurious behavior (SIB) among individuals with intellectual and developmental disabilities (IDD). In behavioral models of SIB, sensory mechanisms function as positive or negative automatic reinforcers, but there is little evidence directly linking behavioral and biological mechanisms. Evidence from both clinical and animal studies of chronic pain supports the hypothesis that some forms of SIB may be regulated by altered pain mechanisms. Past research has shown that pain can lead to SIB in the IDD population but we know almost nothing about whether chronic SIB leads to pain and the resulting neuro-immune cascade of effects. An established body of preclinical and clinical literature and the investigator's preliminary data provide initial support for a working sensory dysfunction and neuropathic-pain like hypothesis of chronic SIB and point to an important role for the peripheral and central mechanisms of pain and inflammatory/immune activity. The purpose of this project is to begin testing a novel model of SIB in relation to chronic neuropathic-like pain due to inflammatory and immune system activation. We hypothesize that there will be a subgroup of individuals with chronic SIB that have significantly (a) altered peripheral sensory innervation, (b) increased inflammatory and immune activity, and (c) increased immune-mediated 'sickness' like behavior. A case-control design will be used to compare matched (age, gender, IQ) groups of children with IDD with (n = 40) and without SIB (n = 40). The groups will be compared on measures of (a) peripheral innervation (Aim 1), (b) inflammatory/immune cytokines and related peptides (Aim 2), and (c) functional indicators of 'sickness'-like behavior including adaptive/social behavior, sleeping/eating, and sensory reactivity and pain signs/symptoms as well as within SIB group comparisons of functional and structural variables (Aim 3). This study will provide the first opportunity to systematically investigate neuro-immune variables in relation to SIB among children with IDD. $383,231.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Federal University of Minnesota Minnesota New http://projectreporter.nih.gov/project_info_description.cfm?aid=7784611&icde=8906142 No URL available. No URL available. active 2010-2015
Project Id: 3530 5R01NS045217-07 None National Institutes of Health Rudy, Bernardo Molecular components of A-type K+ channels This project investigates the relevance of newly discovered components of ion channels in brain neurons that are important in learning, pain control, and the pathogenesis of epilepsy and autism. Fast transient potassium currents, such as those found in neurons and cardiac cells, are essential for the proper functioning of the brain and the heart. During pathological conditions, abnormalities in these currents can contribute to disease conditions. This project addresses the molecular nature of the ion channels responsible for the generation of these currents in mammalian neurons, using both cellular and mouse models. It seeks to establish the molecular composition of these channels and to elucidate the physiological significance of the identified components. $349,013.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Federal New York University School of Medicine New York Ongoing http://projectreporter.nih.gov/project_info_description.cfm?aid=7761294&icde=8914109 No URL available. No URL available. active 2009-2014
Project Id: 3177 2010-14 None Autism Research Institute Samuel, Arthur Multidimensional impact of pain on individuals and family functioning in ASD The funds will cover the cost of administering scales, coordinating medical staff, disseminating materials, and analyzing data for this study on the multidimensional impact of pain on individuals with autism spectrum disorders. $15,000.00 Biology Question 2: Other Dot not applicable No Private The Research Foundation of the State University of New York New York New No URL available. No URL available. No URL available. active 2010-2011
Project Id: 3531 1ZIAMH002914-03 None National Institutes of Health Swedo, Susan Treatment of medical conditions among individuals with autism spectrum disorders The life-long impairments in communication and social function for those with autism are often complicated by the presence of medical comorbidities, including epilepsy, gastrointestinal disturbances, and sleep disorders. Little is known about the pathophysiology of these comorbid conditions and even less about treatment of the symptoms among individuals with autism. Sleep disorders in ASD are of particular interest and can be reliably investigated using polysomnography (PSG), a non-invasive recording of a variety of sleep parameters. A previous study showed that children with autism spend an abnormally short time in the Rapid Eye Movement (REM) stage of sleep, which is thought to play a key role in learning and memory, compared to total sleep time. Donepezil hydrochloride is a drug that has been shown to normalize REM sleep, and treatment with donepezil could benefit the quality of sleep in children with autism as well as enhance their ability to learn and remember. This pilot study aims to determine the dose of donepezil that reliably increases the percentage of REM sleep and to assess any potential side effects in children ages 2-11. If donepezil is effective in normalizing REM sleep, and the drug's side-effects profile is favorable, then a placebo-controlled trial will be initiated to assess the effects of long-term donepezil administration on REM sleep and on autistic symptoms, learning, memory, and overall behavior. $578,006.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Federal National Institutes of Health Maryland Ongoing http://projectreporter.nih.gov/project_info_description.cfm?aid=8158153&icde=8917122 No URL available. No URL available. active Ongoing
Project Id: 3525 5R01HD065282-02 None National Institutes of Health Castellanos, Francisco Neural dissection of hyperactivity/inattention in autism Although many school-age children with autism spectrum disorders are also hyperactive and inattentive, which further limits their school and social functioning, researchers have been unable to determine whether the brain processes responsible for such ADHD-like symptoms are the same as in typical ADHD or whether they reflect distinct brain processes. Using new functional magnetic resonance imaging (fMRI) methods to measure spontaneous brain function (functional connectivity of neural circuits), this study will disentangle these issues in three groups of children: children with an autism spectrum disorder diagnosis, children with ADHD, and typically developing children to use as experimental controls. If successful, the types of brain mechanisms that are involved in hyperactivity and inattention in children with autism will be better understood, and then this new knowledge can be applied to guide targeted treatment studies. $1,117,595.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. Yes Federal New York University School of Medicine New York Ongoing http://projectreporter.nih.gov/project_info_description.cfm?aid=7943093&icde=6667667 No URL available. No URL available. active 2009-2011
Project Id: 3528 5DP1OD003347-04 None National Institutes of Health Jensen, Frances Understanding the cognitive impact of early life epilepsy There is clinical evidence that early life seizures may be one of many precedents for autism, and epilepsy is common in patients with autism, suggesting an interaction between the two processes. In this study, researchers will induce seizure activity in young rats in order to determine whether early life seizures lead to cognitive dysfunction similar to that observed in autism. The researchers will also test whether different drug interventions administered after the seizure can help lessen neuronal damage caused by seizures. This study may uncover crucial biological connections between epilepsy and autism and identify therapeutic agents that could one day be used to treat these overlapping conditions. $845,000.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Federal Children's Hospital Boston Massachusetts Ongoing http://projectreporter.nih.gov/project_info_description.cfm?aid=7914219&icde=8954496 No URL available. No URL available. active 2007-2012
Project Id: 3529 5R21HD065289-02 None National Institutes of Health Levitt, Pat The MET signaling system, autism and gastrointestinal dysfunction In this project, researchers will directly investigate relationships between co-occurring gastrointestinal dysfunction (GID) and autism spectrum disorders (ASD), testing a biological hypothesis regarding disruption of the tyrosine kinase receptor MET receptor and its associated intracellular signaling events as a common theme in ASD. Genetic polymorphisms in MET have been implicated in ASD, and MET plays a role in brain wiring and gastrointestinal epithelial cell repair. Researchers will follow a pediatric group with and without ASD, characterizing their GI function and genotyping for sequence alterations in the MET gene to connect the genetic risk findings with biological changes. The studies will provide unique epidemiological descriptions of the study population giving insight into stratification of the ASD subgroup that is characterized by the presence of GID. Identification of biomarkers such as pan-MET and phospho-MET protein levels may also benefit diagnosis and treatment for ASD. $277,299.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. Yes Federal University of Southern California California Ongoing http://projectreporter.nih.gov/project_info_description.cfm?aid=7938848&icde=8942995 No URL available. No URL available. active 2009-2011
Project Id: 3524 AR080087 None Department of Defense Mong, Jessica Etiology of sleep disorders in ASD: Role of inflammatory cytokines Although sleep problems are not a diagnostic determinant for autism, children diagnosed with Autism Spectrum Disorders (ASD) experience high rates of sleep disorders that typically include night-time hyper-vigilances (night-time arousals). There have been relatively few reports that address the underlying cause for these disruptions. Alterations in sleep have been linked with cognitive and behavioral deficits as well as stress and anxiety. The initiation of the stress axis may feed back and exacerbate the sleep dysregulation, which may further worsen the behavioral deficits. A consequence of increased anxiety is a dysregulation of cytokines, which are cellular signaling molecules. Long-term exposure to high levels of cytokines can disrupt sleep patterns. Elevated cytokine levels have been reported in children with ASD. To date, the current animal models of ASD have not been utilized to investigate the underlying causes of sleep disturbances. This proposal will test the prediction that increased levels of proinflammatory cytokines are present in an animal model of ASD and these cytokines underlie the dysregulation of sleep patterns. Prenatal exposure to valproic acid (VPA) is an accepted rodent model of ASD as it parallels both neuroanatomical and functional (i.e., behavioral) pathologies associated with ASD. First, we will determine if changes in sleep architecture correlate with altered cytokine levels in the VPA model. If so, we will test whether blockade of aberrant cytokine action alters sleep patterns and attenuates adverse behavioral consequences associated with ASD in the VPA animal model. Identifying and understanding the sleep disorders that are potentially compounding autistic behaviors may have a favorable outcome on treatment. $0.00 Biology Question 2: Short-term Objective E Green dot: Objective has greater than or equal to the recommended funding. No Federal University of Maryland, Baltimore Maryland Ongoing http://cdmrp.army.mil/search.aspx No URL available. No URL available. active 2009-2011
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